Intrahepatic Cholestasis of Pregnancy (ICP) is an serious liver condition in pregnancy. The main symptom of this is itching. Ursodeoxycholic acid is routinely used to treat cholestasis but is not effective in reducing itch in all people who take it. Rifampcin has been used to reduce itch in people with Primary Biliary Cholangitis. This study will randomly allocate women with severe early onset ICP to receive either Ursodeoxycholic Acid, or the "Investigational drug" Rifampicin.
Conditions
Interventions
Product Name: Rifampicin
Pharmaceutical Form: Film-coated tablet
Product Name: Ursodeoxycholic acid
Pharmaceutical Form: Capsule, hard
Sponsors
The University of Adelaide
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Women will be considered eligible for inclusion into the trial with the following criteria: • Severe ICP (defined as pruritus with raised total serum BA =40 µmol/L) confirmed (see note below on standardisation of bile acid assays) • Viable pregnancy between 14+0 and 33+6 weeks gestation inclusive (see note below on gestational age) • No known lethal fetal anomaly • Singleton pregnancy • Obstetric care in a consultant-led unit • Aged 18 years or over • Written informed consent has been obtained Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 108 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: A potential participant who meets any of the following criteria will be excluded from participation in this study: • A decision has already been made for delivery within the next 48 hours • There is allergy to any component of the UDCA or RIF tablets • The woman is taking other medication that has a significant interaction with rifampicin treatment • There is a multi-fetal gestation • There is laboratory-confirmed active hepatitis A or hepatitis B, or positive serology for hepatitis C • There is current pre-eclampsia (ISSHP criteria) • There is a known primary hepatic disorder, including a-1-antitrypsin deficiency and autoimmune hepatitis, including primary biliary cholangitis • The woman is on current medication causing deranged liver enzymes • The woman is unwilling for her baby to have standard Vitamin K administration at birth • The woman has previously participated in TURRIFIC
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare Rifampicin (RIF) with the standard treatment, Ursodeoxycholic acid (UDCA) for the reduction of itch, the main symptom of the disease.;Secondary Objective: 1. To compare the effect of RIF treatment with UDCA on short-term outcomes for both mother and infant including the length of gestation and the incidence of caesarean section and preterm birth 2. To compare the effect of RIF treatment with UDCA on serum concentrations of: bile acids, transaminases, and on metabolites such as serum autotaxin and progesterone sulphated metabolites, and urine glucuronidated 6a-hydroxylated BA. 3. To assess the effect of RIF and UDCA on the metabolome and the microbiome 4. T o assess the effect of treatment with the RIF compared with UDCA on maternal and fetal outcomes analysed by bile acid transporter genotype.;Primary end point(s): Pruritus, defined as worst itch in the previous 24 hours assessed on a patient-recorded visual analogue scale.;Timepoint(s) of evaluation of this end point: At study entry, one week post randomisation, then monthly up to delivery, with optional assessments on a weekly basis after 28 weeks gestation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Outcomes for both mother and infant including the length of gestation and the incidence of caesarean section and preterm birth. 2. Serum concentrations of: bile acids, transaminases, and on metabolites such as serum autotaxin and progesterone sulphated metabolites, and urine glucuronidated 6a-hydroxylated BA, 3. Metabolome and the microbiome. 4. Maternal and fetal outcomes analysed by bile acid transporter genotype ;Timepoint(s) of evaluation of this end point: These numbers correspond to the secondary outcomes listed in E.5.2 above. 1. assessed at delivery 2. to be assessed at study entry, one week post randomisation then on a monthly basis up to delivery. 3. to be assessed at study entry, one week post randomisation then on a monthly basis up to delivery, one and two weeks post delivery 4. to be assessed once for mother using sample collected at study entry, once for baby using sample collected at birth. | — |
Countries
Australia, Finland, Netherlands, Sweden, United Kingdom
Contacts
Public ContactPhysician In Chief
Helsinki University
Outcome results
None listed